It is known to prepare a calcium phosphate hydraulic cement by mixing water or an aqueous phase with a powder composed of various precursors of calcium phosphate. For example, M. Bohner (Injury, 2000, 31:S-D37-47) describes the preparation of hydraulic cements from a mixture of a calcium phosphate possessing an acidic nature and of a calcium phosphate possessing a basic nature. Such cements are available commercially, in particular under the names BoneSource®, Cementek®, Calcibon® or ChronoS Inject®. One of the disadvantages of these cements is that they are resorbed very slowly.
Various routes have been explored to improve the rate of resorption of hydraulic cements.
It has been envisaged to partially replace the calcium of the calcium phosphate compounds by strontium. Thus, GB-943678 discloses calcium phosphate hydraulic cements obtained from a powder composed of a mixture of anhydrous M(H2PO4)2 and of an oxide of a metal M′ (it being possible for M and M′ to represent, independently of one another, Zn, Mg, Ba, Ca, Al, Cd or Sr) in approximately equal proportions by weight, said powder being mixed with water in a water/powder ratio of 0.15 ml/g. The only compositions illustrated are Ca(H2PO4)2+ZnO, on the one hand, Zn(H2PO4)2+ZnO. The cements obtained from these powders have a compressive strength of greater than 100 MPa and setting times of the order of 8-10 min. However, the inventors of the present invention have carried out tests with a mixture of anhydrous calcium bis(dihydrogenphosphate) (Ca(H2PO4)2) and of CaO with an L/P ratio of 1 ml/g, in order to obtain a paste which can be worked under the conditions disclosed in GB-943678, and the results obtained show that the compressive strength after 24 h is less than 1 MPa. The general teaching of this document thus does not make it possible to obtain a cement exhibiting the required properties (good compressive strength, high setting rate) for any combination of M and M′. In addition, in the specific case in which one of the metals M or M′ would be Sr (not illustrated in GB943678), neither the compound Sr(H2PO4)2 nor the compound SrO would make possible the formation of a mean porosity.
Leroux, et al. (Bioceramics, 13, Trans Tech Publications, Switzerland, 2001, 235-238) describe a cement comprising up to 4.3% by weight of Sr, corresponding to a final cement composition Ca9.75Sr0.25(PO4)6(OH)2. This composition can be obtained by adding strontium nitrate Sr(NO3)2 to the liquid phase of the abovementioned Cementek® cement, the solid phase of which is composed of a mixture of α−Ca3(PO4)2 (or α−TCP), of tetracalcium phosphate (or TTCP) and of glycerophosphate. Here again, the specific choice of the strontium precursor does not make it possible to obtain a mean porosity.
Another solution envisaged for improving the rate of resorption of the bone replacement is based on the principle that the presence of interconnected macropores in the calcium phosphate material promotes passive resorption by dissolution of the implant, by allowing it to be percolated by biological fluids, and active resorption by osteoclasts, by allowing them to penetrate into the macropores which are sufficiently large, that is to say greater than 100 μm in size. U.S. Pat. No. 6,547,866 discloses porous calcium phosphate materials obtained by adding, to the composition, compounds which release a gas during the setting of the cement (carbonate+citric acid, which release CO2, hydrogen peroxide, which releases O2). However, the pores obtained have a relatively small mean size and the mechanical strength is reduced. In addition, it has been proposed to prepare calcium phosphate materials by addition to the composition, before the setting thereof, of a water-soluble compound of the NaHCO3, Na2HPO4, sucrose or mannitol type (Markovic et al., Bioceramics, Trans Tech Publications, Switzerland, 2001, 773-775; Takagi and Chow, J. Mater. Sci. Mater. Mad., 2001, 13, 135-139). The dissolution of these sugars interferes with the setting of the cement, which greatly reduces the crushing strength.
The addition of particles or of fibers of a biodegradable polymer has also been envisaged. Simon et al. (J. Orthop. Res., 2002, 25, 473-482) describe cements of the BoneSource® type, obtained from TTCP, which is a basic phosphate, and from anhydrous dicalcium phosphate (DCPA), which is an acidic phosphate, and poly(lactide-co-glycolide) PLAGA microspheres, the rapid decomposition of said polymer giving a macroporosity. However, the mineral part is not degraded in vitro after 90 days.
Xu H et al. (Biomaterials, 2002, 23, 193-202, and Biomaterials, 2004, 25, 1029-1037) describe a calcium phosphate cement (BoneSource®) comprising fibers of Vicryl® or a net of Vicryl®, which is a bioresorbable polymer very rich in glycolic acid. Due to the presence of the fibers or of the net, this cement cannot be injected.
Ruhe et al. (J. Bone Joint Surg., 2003, 85, 75-81) describe a Calcibon® (α−TCP+DCPA+CaCO3+HA) cement comprising PLAGA microspheres charged with rhBMP-2, which diffuses from the polymer (HA denoting hydroxyapatite). However, the authors indicate that the introduction of the polymer very strongly reduces the crushing strength, which changes from 38.6 to 6.4 MPa (value lower than that of trabecular bone≈10 MPa). However, the authors do not indicate whether, after 28 days in pH 7 buffer solution, the polymer and/or the mineral part of the cement are decomposed.